Interferon-alpha downregulates expression of the oxytocin receptor in cultured human myometrial cells

被引:15
作者
Maggi, M [1 ]
Peri, A [1 ]
Baldi, E [1 ]
Mancina, R [1 ]
Granchi, S [1 ]
Fantoni, G [1 ]
Finetti, G [1 ]
Forti, G [1 ]
Raggi, CC [1 ]
Serio, M [1 ]
机构
[1] UNIV FLORENCE, DEPT CLIN PHYSIOPATHOL, ANDROL & ENDOCRINOL UNIT, I-50139 FLORENCE, ITALY
来源
AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM | 1996年 / 271卷 / 05期
关键词
uterus; cytokine; calcium; binding;
D O I
10.1152/ajpendo.1996.271.5.E840
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Previous studies in the endometrium of ruminants showed that type I interferon (IFN) prevents oxytocin receptor (OTR) formation. We studied the effect of IFN-alpha on human myometrial cells in culture expressing a high density of biologically active OTR. We found that IFN-alpha induced a 35-50% decrease in OTR mRNA and protein and that this inhibition was time and dose dependent. Maximal inhibition of OTR mRNA was obtained after 2-3 days, whereas 1-(beta-mercapto-beta,beta-cyclopentamethylenepropionic acid,2-O-Me-Tyr,Thr(4),Orn(8),Tyr(9)-amide)-[I-125]vasotocin ([I-125]OTA) binding reached a nadir after 3-4 days, with half-maximal inhibitory concentration (IC50) = 1,100 U/ml. Mathematical analysis of multiple homologous competition curves for [I-125]OTA indicated that IFN-alpha treatment (5.000 U/ml x 3 days) reduced just the binding capacity (B-max) without changing the binding affinity. Accordingly the same treatment with IFN-alpha did not affect the half-maximally effective concentration (EC(50)) for the oxytocin-induced increase in intracellular calcium but significantly decreased maximal responsiveness (E(max)) of myometrial cells to OT stimulation. In conclusion, our data demonstrate. for the first time, a negative regulation by IFN-alpha of the steady-state expression of OTR mRNA in cultured human myometrial cells obtained from nonpregnant uteri. This inhibition was followed by a parallel decrease in both the B-max for [I-125]OTA and E(max) for oxytocin, suggesting a decreased OTR protein availability.
引用
收藏
页码:E840 / E846
页数:7
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